The proposed studies are aimed at extending our investigations on the possible role of microbial agents in the causation of major congenital malformations and/or significant acute clinical manifestations in the newborn. Electron microscopy (EM) and immune electron microscopy (IEM) will be applied to: (a) detect viruses (old or new) in the affected infant's urine, serum, cerebrospinal and/or ventricular fluid, throat or stool, which cannot be identified by more conventional virological techniques; (b) obtain a more rapid diagnosis of agents already known to be involved with these conditions, e.g. cytomegalovirus. Maternal serum will be particularly valuable to test by IEM, since the mother would be expected to have been infected with the putative agent involving her fetus. Any virus detected by these techniques will be: (a) studied as regards its possible causality to the disease process; (b) identified by its size, morphological and biochemical characteristics and by its effect in various tissue culture and animal systems. Infants will be followed by laboratory, clinical and epidemiological means to establish the consequences of such an infection. The long-term goals of these investigations is to improve diagnosis, so as to permit earlier preventive and therapeutic measures, as well as to find newer agents that might be involved in major congenital malformations which affect at least 1% of all deliveries and for which a known cause (genetic, chromosomal or environmental) can be found in less than 5% of cases.